A novel HIF-1 inhibitor--manassantin A derivative LXY6099 inhibits tumor growth / 药学学报
Acta Pharmaceutica Sinica
;
(12): 622-626, 2014.
Artigo
em Chinês
| WPRIM
| ID: wpr-245037
ABSTRACT
Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor on hypoxia responses in mammalian tissues. HIF-1 plays as a positive factor in solid tumor and leads to hypoxia-driven responses that enhance its downstream gene expression for tumor growth and survival. LXY6099 was obtained by the structural modification and optimization of manassantin A (MA) as a high potent HIF-1 inhibitor. Antitumor activity of LXY6099 was observed in this study. LXY6099 with an IC50 value of 2.46 x 10(-10) mol x L(-1) showed more sensitive inhibition activity to HIF-1 than that of MA detected by reporter gene assay (> 100 folds). It showed strong inhibition on the growth of human solid tumor cell lines. Furthermore, LXY6099 exhibited significant antitumor activity against established human tumor xenografts in nu/nu mice with treatment of MX-1 breast cancer. Thus, LXY6099 as a novel HIF-1 inhibitor could be further developed into anti-cancer agents.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Farmacologia
/
Neoplasias da Mama
/
Regulação Neoplásica da Expressão Gênica
/
Lignanas
/
Linhagem Celular Tumoral
/
Fator 1 Induzível por Hipóxia
/
Xenoenxertos
/
Metabolismo
/
Camundongos Nus
/
Antineoplásicos
Limite:
Animais
/
Humanos
Idioma:
Chinês
Revista:
Acta Pharmaceutica Sinica
Ano de publicação:
2014
Tipo de documento:
Artigo
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